Meropenem 500 Mg/000 Mg Solution

MEROPENEM FRESENIUS is indicated for treatment of the following infections, caused by single or multiple susceptible bacteria and as empiric therapy prior to the identification of the causative organisms:

• Acute exacerbation of chronic bronchitis and pneumonia due to: Staphylococcus aureus (methicillin susceptible strains only), Streptococcus pneumoniae, Streptococcus spp., Escherichia coli, Haemophilus influenzae, Haemophilus parainfluenzae, Pseudomonas aeruginosa, Moraxella (Branhamella) catarrhalis, Klebsiella spp, Enterobacter cloacae, Enterobacter spp., Acinetobacter spp.
• Pneumonia in children due to: Staphylococcus aureus (methicillin susceptible strains only), Streptococcus pneumoniae, Haemophilus influenzae, Pseudomonas aeruginosa
• Urinary tract infections in adults and children, including complicating infections due to: Enterobacter cloacae, Escherichia coli, Morganella morganii, Proteus mirabilis, Pseudomonas aeruginosa, Serratia marcescens, Citrobacter freundii
• Pelvic inflammatory disease (including tubo-ovarian abscess) and endometritis due to: Enterococcus faecalis, Staphylococcus aureus (methicillin susceptible strains only), coagulase-negative Staphylococcus spp. (methicillin susceptible strains only), Streptococcus agalactiae Group B, Streptococcus viridans, Streptococcus spp., Escherichia coli, Neisseria gonorrhoeae, Klebsiella pneumoniae, Enterobacter aerogenes, Enterobacter cloacae, Proteus mirabilis, Acinetobacter anitratus, Acinetobacter lwoffii, Gardnerella vaginalis, Bacteroides fragilis group, Peptostreptococcus anaerobius, Peptostreptococcus asaccharolyticus, Peptostreptococcus magnus
• Skin and skin structure infections in adults due to: Staphylococcus aureus (methicillin susceptible strains only), coagulase-negative Staphylococcus spp, Streptococcus pyogenes (Group A), Streptococcus agalactiae, Streptococcus viridans, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Bacteroides fragilis, Peptostreptococcus spp.
• Meningitis in adults and children due to: Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitides
• Septicaemia in adults and children due to: Streptococcus pneumoniae, Escherichia coli, Klebsiella pneumonia
• Empiric treatment, including initial monotherapy, for presumed bacterial infections in host-compromised neutropenic patients due to: Streptococcus epidermidis, Streptococcus mitis, Streptococcus sanguinis, Escherichia coli
• Intra-abdominal abscess and peritonitis due to: Streptococcus milleri, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Pseudomonas aeruginosa, Bacteroides fragilis group (including Bacteroides distasonis, Bacteroides fragilis, Bacteroides ovatus, Bacteroides thetaiotaomicron, Bacteroides vulgatus), Clostridium perfringens, Streptococcus mitior
• Polymicrobial infections

Note: In the treatment of infections caused by Pseudomonas aeruginosa, an aminoglycoside should be administered concomitantly.

Posology

Adult dosage schedule (normal renal function)

Intravenous administration: Usually, 500 mg to 1 000 mg is administered every 8 hours, based on the type or severity of the infection, the known or suspected susceptibility of the pathogen(s) and the condition of the patient. See section 4.1 for types of infections and in vivo susceptible organisms.

Exceptions:

• Febrile episodes in neutropenic patients u2013 the dose should be 1 000 mg every 8 hours.
• Meningitis u2013 the dose should be 2 000 mg every 8 hours.

Caution may be required in using beta-lactam antibiotics in critically ill patients with known or suspected Pseudomonas aeruginosa lower respiratory tract infections. Concomitant use of an aminoglycoside is recommended. Regular sensitivity testing is recommended when treating Pseudomonas aeruginosa.

Dosage schedule for adults with impaired renal function

The dosage should be reduced in patients with creatinine clearance less than 51 mL/minute, as scheduled below.

Creatinine clearance (mL) Dose (based on u201cunitu201d dose range of 500 mg to 2 000 mg every 8 hours u2013 see above) Frequency

• 26 u2013 50 one unit dose every 12 hours
• 10 -25 half the unit dose every 12 hours
• < 10 half the unit dose every 24 hours

Dosage for the treatment of adults on haemodialysis: MEROPENEM FRESENIUS is cleared from the circulation during haemodialysis. If continued treatment with MEROPENEM FRESENIUS is necessary, the required dose should be used at completion of the haemodialysis cycle to re-institute effective treatment. There is no experience with peritoneal dialysis.

Adults with hepatic insufficiency

No dosage adjustment is necessary in patients with impaired hepatic metabolism.

Elderly

No dosage adjustment is required for the elderly with normal renal function or creatinine clearance values above 50 mL/minute.

Paediatric population

Safety and efficacy in babies under 3 months have not been established. Infants and children from 3 months to 12 years: 10 u2013 40 mg/kg every 8 hours, depending on the type and severity of the infection, the suspected susceptibility of the pathogens and condition of the patient. Children > 50 kg: The dosage as indicated for adults should be used.

EXCEPTION: Meningitis: 40 mg/kg every 8 hours. There is no experience in children with renal impairment.

Method of administration

MEROPENEM FRESENIUS should be given as an intravenous bolus injection over approximately 5 minutes or by intravenous infusion over approximately 15-30 minutes after dissolving the sterile powder. For instructions on reconstitution of MEROPENEM FRESENIUS before administration, see section 6.6. For further dilution for infusion, see section 6.6 (see instructions for compatibility and stability in sections 6.2, 6.3 and 6.6). The reconstituted solution for infusion is a clear, colourless to pale yellow solution, free from visible particulate matter.

• Hypersensitivity to meropenem or any component of MEROPENEM FRESENIUS.
• History of hypersensitivity to carbapenems, penicillins, cephalosporins or other beta-lactam antibiotics.

Prescribers must adhere to the principles of antibiotic stewardship. The selection of MEROPENEM FRESENIUS to treat an individual patient should consider the appropriateness of using a carbapenem antibacterial medicine based on factors such as severity of the infection, the prevalence of resistance to other suitable antibacterial medicines and the risk of selecting for carbapenem-resistant bacteria. See section 5.1.

Hypersensitivity reactions

Serious and occasionally fatal hypersensitivity reactions have been reported (see section 4.8). Patients who have a history of hypersensitivity to carbapenems, penicillins or other beta-lactam antibiotics may also be hypersensitive to meropenem (see section 4.3). Before initiating therapy with MEROPENEM FRESENIUS, careful inquiry should be made concerning previous hypersensitivity reactions to beta-lactam antibiotics. If a severe allergic reaction occurs, MEROPENEM FRESENIUS should be discontinued and appropriate measures taken. Severe cutaneous adverse reactions (SCAR), such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN), drug reaction with eosinophilia and systemic symptoms (DRESS), erythema multiforme (EM) and acute generalised exanthematous pustulosis (AGEP) have been reported in patients receiving meropenem (see section 4.8). If signs and symptoms suggestive of these reactions appear, MEROPENEM FRESENIUS should be withdrawn immediately and an alternative treatment should be considered.

Antibiotic-associated colitis

Antibiotic-associated colitis and pseudomembranous colitis have been reported with nearly all antibacterial medicines, including meropenem, and may range in severity from mild to life threatening. Therefore, it is important to consider this diagnosis in patients who present with diarrhoea during or subsequent to the administration of MEROPENEM FRESENIUS (see section 4.8). Discontinuation of therapy with MEROPENEM FRESENIUS and the administration of specific treatment for Clostridium difficile should be considered. Medicines that inhibit peristalsis should not be given.

Seizures

Seizures have infrequently been reported during treatment with carbapenems, including MEROPENEM FRESENIUS (see section 4.8).

Hepatic function monitoring

Hepatic function should be closely monitored during treatment with MEROPENEM FRESENIUS due to the risk of hepatic toxicity (hepatic dysfunction with cholestasis and cytolysis) (see section 4.8). Patients with pre-existing liver disorders should have their liver function monitored during treatment with meropenem. There is no dose adjustment necessary (see section 4.2).

Direct antiglobulin test (Coombs test) seroconversion

A positive direct or indirect Coombs test may develop during treatment with MEROPENEM FRESENIUS.

Concomitant use with valproic acid/sodium valproate/valpromide

The concomitant use of MEROPENEM FRESENIUS and valproic acid/sodium valproate/valpromide is not recommended (see section 4.5).

Paediatric population

Efficacy and tolerability in infants under 3 months of age have not been established, therefore, MEROPENEM FRESENIUS is only approved for children over 3 months of age.

MEROPENEM FRESENIUS contains sodium

MEROPENEM 500 mg FRESENIUS contains approximately 2,0 mmol of sodium per 500 mg dose which should be taken into consideration by patients on a controlled sodium diet. MEROPENEM 1 000 mg FRESENIUS contains approximately 4,0 mmol of sodium per 1 000 mg dose which should be taken into consideration by patients on a controlled sodium diet.

No specific medicine interaction studies other than probenecid were conducted. The potential effect of meropenem on the protein binding of other medicines or metabolism has not been studied. However, the protein binding is so low that no interactions with other compounds would be expected based on this mechanism.

Probenecid

Probenecid competes with MEROPENEM FRESENIUS for active tubular secretion and thus inhibits the renal excretion of meropenem with the effect of increasing the elimination half-life and plasma concentration of meropenem. Caution is required if probenecid is co-administered with MEROPENEM FRESENIUS.

Valproate/valproic acid

Decreases in blood levels of valproic acid have been reported when it is co-administered with carbapenem medicines (including MEROPENEM FRESENIUS) resulting in a 60-100 % decrease in valproic acid levels in about two days. Subtherapeutic levels may be reached. Due to the rapid onset and the extent of the decrease, co-administration of valproic acid/sodium valproate/valpromide with MEROPENEM FRESENIUS is not considered to be manageable and therefore should be avoided (see section 4.4).

Oral anti-coagulants

Simultaneous administration of MEROPENEM FRESENIUS with warfarin may augment its anti-coagulant effects. There have been many reports of increases in the anti-coagulant effects of orally administered anti-coagulant medicines, including warfarin, in patients who are concomitantly receiving antibacterial medicines. The risk may vary with the underlying infection, age, and general status of the patient so that the contribution of the antibiotic to the increase in INR (international normalised ratio) is difficult to assess. It is recommended that the INR should be monitored frequently during and shortly after co-administration of antibiotics with an oral anti-coagulant.

Paediatric population

Interaction studies have only been performed in adults.

Pregnancy

The safety in pregnant women has not been established. MEROPENEM FRESENIUS should therefore not be used during pregnancy.

Breastfeeding

Meropenem (contained in MEROPENEM FRESENIUS) is detectable in small quantities in human breast milk. MEROPENEM FRESENIUS should not be used in breastfeeding mothers, or mothers should not breastfeed their babies if treatment with MEROPENEM FRESENIUS is deemed essential for them.

When driving or operating machines, it should be considered that headache, paraesthesia and convulsions have been reported for meropenem.

Summary of the safety profile

Meropenem-related adverse reactions most frequently reported were diarrhoea, rash, nausea/vomiting and injection site inflammation. The most frequently reported meropenem-related laboratory adverse events were thrombocytosis and increased hepatic enzymes.

Tabulated summary of adverse reactions

In the table below all adverse reactions are listed by system organ class and frequency: frequent; less frequent; and not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.

Paediatric population

MEROPENEM FRESENIUS is approved for children over 3 months of age. There is no evidence of an increased risk of adverse reactions in children.

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicine is important. It allows continued monitoring of the benefit/risk balance of the medicine. Health care providers are requested to report any suspected adverse drug reactions to SAHPRA via the Med Safety APP (Medsafety X SAHPRA) and eReporting platform (who-umc.org) found on SAHPRA website. Healthcare providers are asked to report any suspected adverse drug reactions to the Holder of the Certificate of Registration at the following email address: [email protected] and to the relevant medicineu2019s regulatory authority in the country where the product is marketed.

In overdose, side effects can be precipitated and/or be of increased severity (see section 4.8). In patients with renal impairment relative overdosage is possible if the dose is not adjusted as described in section 4.2. Treatment is symptomatic and supportive. Patients with normal renal function should have rapid renal elimination. In patients with renal impairment, haemodialysis will remove MEROPENEM FRESENIUS and its metabolite.